Scores were lower than group 4 (Scheffe post hoc tests, p,0.01). ?Sex (Male/Female) Age (years) Age at onset (years) Disease Duration (months) UPDRS-III Tremor Score Bradikynesia Score Axial Score Progression rate MMSE FAB HADS HADS-D HADS-A Total NMS per patient Total NMS-D per patient59/41 59.768.3 58.468.7 13.465.6 15.367.4 1.7261.58 4.9863.45 3.8962.19 1.4161.12 27.0761.98 13.861.88 11.4965.36 5.8563.01 5.6462.94 4.362.9 2.9361.Group 4: Motor DominantTwenty patients (20 ) with a mean age of 63.767.9 years constituted the group. Patients grouped in this cluster showed the highest UPDRS III, Bradykinesia and Axial scores, Progression rate, HADS and HADS-D (Scheffe post hoc tests, p,0.01). Group ?4 was associated with bilateral involvement (Fisher’s Exact test, p,0.01). Age and Age at onset were higher than in group 1 (Scheffe post hoc tests, p,0.01). There was a negative association ?between patients included in this group and a positive familial history (Fisher’s Exact test, p,0.01). Tremor score was found to be higher than group 1 (Scheffe post hoc tests, p,0.01). Number of ?NMS-D were significantly lower than group 3 (Scheffe post hoc ?tests, p,0.01), but higher than groups 1 (Scheffe post hoc tests, ?p,0.01). FAB was significantly lower than group 2 (Scheffe post ?hoc tests, p,0.01). Table 4 summarizes the characteristics of the four groups of patients identified through the cluster analysis. Data obtained from the 2-year follow up evaluation have been used mainly to test the a priori hypothesis that the “Motor Dominant” subgroup would have progressed faster in terms of motor scores, requiring higher LEDD. Such data are detailed in table 2B. Briefly, “Motor Dominant” group showed a more severe progression of UPDRS III, bradykinesia, and axial scores (Anova test for repeated Title Loaded From File measures, p,0.01) and required higher LEDD (t-test, p,0.01) compared to all other clusters. Moreover, an higher proportion of patients belonging to this cluster was on L-Dopa, compared to all other groups (9 out of 20, i.e. 45 vs 5 , 3 and 25 , respectively; chi2-test, p,0.01). The logistic regression showed that UPDRS III (b coefficient = 0.51; 95 CI:[0.36;0.64]; p,0.001), Sex Domain (b coefficient = -5.16; 95 CI:[27.49; 22.81]; p,0.001) and Acting out during dreams (b coefficient = 1.04; 95 CI:[0.18;2.13]; p,0.05) classified 50 of patients into the correct cluster (pseudo-R2 = 0.499).Abb. UPDRS-III: Unified Parkinson’s Disease Rating Scale, motor section; MMSE: Mini Mental State Examination; FAB: Frontal Assessment battery; HADS: Hospital Anxiety Depression Scale; HADS-D: Hospital Anxiety Depression Scaledepression subscale; HADS-A: Hospital Anxiety Depression Scale-anxiety subscale; NMS: non-motor symptoms; NMS-D: non-motor domains. doi:10.1371/journal.pone.Title Loaded From File 0070244.tThe clustering optimum was attained for the 4 clusters solution (Calinski-Harabasz pseudo-F = 48.53). Table 2A illustrates the mean values of each baseline continuous variable for the four identified clusters, while results of analyses on baseline categorical data are listed in table 3.Group 1: Benign Pure MotorTwenty-one patients (21 ) with a mean age of 55.468.6 23977191 years constituted the group. This group showed the lowest number of NMS and NMS-D compared to all groups (Scheffe post hoc tests, ?p,0.01). Age and Age at onset, FAB, HADS and HADS-D scores were significantly lower than group 4 (Scheffe post hoc tests, ?p,0.01). UPDRS III, Axial score, and Progression rate were lower than grou.Scores were lower than group 4 (Scheffe post hoc tests, p,0.01). ?Sex (Male/Female) Age (years) Age at onset (years) Disease Duration (months) UPDRS-III Tremor Score Bradikynesia Score Axial Score Progression rate MMSE FAB HADS HADS-D HADS-A Total NMS per patient Total NMS-D per patient59/41 59.768.3 58.468.7 13.465.6 15.367.4 1.7261.58 4.9863.45 3.8962.19 1.4161.12 27.0761.98 13.861.88 11.4965.36 5.8563.01 5.6462.94 4.362.9 2.9361.Group 4: Motor DominantTwenty patients (20 ) with a mean age of 63.767.9 years constituted the group. Patients grouped in this cluster showed the highest UPDRS III, Bradykinesia and Axial scores, Progression rate, HADS and HADS-D (Scheffe post hoc tests, p,0.01). Group ?4 was associated with bilateral involvement (Fisher’s Exact test, p,0.01). Age and Age at onset were higher than in group 1 (Scheffe post hoc tests, p,0.01). There was a negative association ?between patients included in this group and a positive familial history (Fisher’s Exact test, p,0.01). Tremor score was found to be higher than group 1 (Scheffe post hoc tests, p,0.01). Number of ?NMS-D were significantly lower than group 3 (Scheffe post hoc ?tests, p,0.01), but higher than groups 1 (Scheffe post hoc tests, ?p,0.01). FAB was significantly lower than group 2 (Scheffe post ?hoc tests, p,0.01). Table 4 summarizes the characteristics of the four groups of patients identified through the cluster analysis. Data obtained from the 2-year follow up evaluation have been used mainly to test the a priori hypothesis that the “Motor Dominant” subgroup would have progressed faster in terms of motor scores, requiring higher LEDD. Such data are detailed in table 2B. Briefly, “Motor Dominant” group showed a more severe progression of UPDRS III, bradykinesia, and axial scores (Anova test for repeated measures, p,0.01) and required higher LEDD (t-test, p,0.01) compared to all other clusters. Moreover, an higher proportion of patients belonging to this cluster was on L-Dopa, compared to all other groups (9 out of 20, i.e. 45 vs 5 , 3 and 25 , respectively; chi2-test, p,0.01). The logistic regression showed that UPDRS III (b coefficient = 0.51; 95 CI:[0.36;0.64]; p,0.001), Sex Domain (b coefficient = -5.16; 95 CI:[27.49; 22.81]; p,0.001) and Acting out during dreams (b coefficient = 1.04; 95 CI:[0.18;2.13]; p,0.05) classified 50 of patients into the correct cluster (pseudo-R2 = 0.499).Abb. UPDRS-III: Unified Parkinson’s Disease Rating Scale, motor section; MMSE: Mini Mental State Examination; FAB: Frontal Assessment battery; HADS: Hospital Anxiety Depression Scale; HADS-D: Hospital Anxiety Depression Scaledepression subscale; HADS-A: Hospital Anxiety Depression Scale-anxiety subscale; NMS: non-motor symptoms; NMS-D: non-motor domains. doi:10.1371/journal.pone.0070244.tThe clustering optimum was attained for the 4 clusters solution (Calinski-Harabasz pseudo-F = 48.53). Table 2A illustrates the mean values of each baseline continuous variable for the four identified clusters, while results of analyses on baseline categorical data are listed in table 3.Group 1: Benign Pure MotorTwenty-one patients (21 ) with a mean age of 55.468.6 23977191 years constituted the group. This group showed the lowest number of NMS and NMS-D compared to all groups (Scheffe post hoc tests, ?p,0.01). Age and Age at onset, FAB, HADS and HADS-D scores were significantly lower than group 4 (Scheffe post hoc tests, ?p,0.01). UPDRS III, Axial score, and Progression rate were lower than grou.
